What Advanced Practitioners Need to Know About HER2 (ERBB2)-Mutant Non–Small Cell Lung Cancer: A Case-Based Approach

Stephanie McDonald: Welcome everybody to this virtual roundtable about HER-mutant non-small cell lung cancer for advanced practitioners. This is a case-based approach. I'm Stephanie McDonald. I'm an oncology nurse practitioner in thoracic oncology from Dana-Farber Cancer Institute in Boston, Massachusetts.

I have over 15 years’ experience in healthcare and caring for patients with cancer. Joining me today is my panel of colleagues, Dr. Narjust Florez and advanced practitioner Sarah Tangerini. I'd like to begin by having my colleagues just take a minute to introduce themselves.

Dr. Narjust Florez: Hello, everyone. I'm Dr. Narjust Florez. I'm a thoracic medical oncologist. We are focused on women. Really happy to be here.

Stephanie McDonald: Thank you.

Sarah Tangerini: Hi, everyone. My name is Sarah Tangerini. I'm a thoracic nurse practitioner at Dana-Farber Cancer Institute in Boston. I work with both Stephanie and Dr. Florez. I've been here at Dana-Farber for three years working with the thoracic oncology group, and prior to this, I worked in clinical research, and I'm happy to be here.

Stephanie McDonald: Thank you. I'm happy for both of you to be here and contribute to our discussion. In this case, the second case that we're going to be going over, we're going to be looking at a patient with lung adenocarcinoma with a HER2 mutation following first line chemo immunotherapy. This is a 57 year old man with no history of smoking. He presents with back pain and shortness of breath.

He was found to have metastatic lung adenocarcinoma. And molecular testing or next generation sequencing panel showed a HER2 exon 20 insertion mutation, and specifically, a PA 775 G776 insertion, YVMA mutation. PD-L1 expression was less than 1%. He ended up receiving first line treatment with pembrolizumab plus carboplatin and pemetrexed, and now has progression of disease after 11 months of treatment.

My first question in this discussion will be directed to Dr. Florez. What would the next steps be in this patient's treatment care now that they've had progression of disease after 11 months of first line standard of care, chemo immunotherapy?

Dr. Narjust Florez: Well first, Stephanie, I give you a lot of credit for actually saying the whole mutation. I don't think I have ever done that in a presentation, so that's very brave.

Stephanie McDonald: Thank you.

Dr. Narjust Florez: First is to explain the patient that the current therapy is not working, and we cannot blame patients for therapy not working. Using language like, "You failed therapy or you progressed," that is not correct. We move for less guilt, blaming to patients and saying, "Sorry, it's no longer working, the therapy failed you." So that's the first thing.

It's a restart. We sit up, we discuss concerns, we discuss fears, and discuss next treatment options. In this case, it will be HER2 directed therapy. Explain the logistics. A lot of ... how often I'm going to get the infusion, where are these infusions going to happen? And why I cannot take a pill? Because for breast cancer, there are pills which do not work in lung cancer. I think that's the first step: reset, address concerns, discuss next steps and provide patients emotional support, because this is a very difficult time for patients and for their families.

Stephanie McDonald: Absolutely. Thank you. And Sarah, what's the role of the advanced practitioner in preparation for starting this new treatment? So they failed ... I take that back. They didn't fail. The therapy failed them. Thank you, Dr. Florez. So what is the role in prepping a patient who is going to be pursuing second line treatment with trastuzumab deruxtecan?

Sarah Tangerini: Sure. So as the advanced practitioner, it's our job to help better prepare our patients so that they know what to expect before starting a new treatment, whether it be standard chemotherapy or targeted therapy. This includes obtaining a detailed patient history, reviewing current medications they are on, and then outlining the treatment schedule, frequency of visits, sometimes the percentage of infusion reactions, and then the baseline tests that are needed prior to starting treatment, and common side effects that they may experience and how we manage these side effects such as antiemetic teaching.

In our practice here at Dana-Farber, our nurse practitioners do scheduled chemotherapy teaching visits prior to starting treatment. And I have found since starting these visits, it has really helped to decrease the anxieties of patients going into a new treatment. A lot of the time, if we don't do these chemotherapy treatment teaching visits ahead of time, our patients come into clinic with a long list of questions. They're calling in prior to starting treatment. They don't know what to expect, and it increases their anxieties.

In order to decrease these anxieties, we like to provide a 60-minute visit with our patients and go over any questions that they may have prior to starting their new treatment.

Stephanie McDonald: Awesome. Agree. I think having an implementation of chemotherapy teaching sessions within our practice with the advanced practitioner, it's gold. It's great for us because we have a better understanding, especially if it's a new patient to the practice, setting the foundation for our relationship going forward, and setting up that team based approach with the advanced practitioner and our physician colleagues, and our nurses, and other staff members.

Like Dr. Florez and Sarah has mentioned, it is a team based approach. But setting that foundation with the chemotherapy teach, especially when a new drug is implemented, it helps cut down patient anxiety, it helps prepare them for the road ahead, it helps them understand, again, what to expect, when to call. It's ideal. I think it should be [...] Hopefully, it is implemented in other institutions, but if it isn't, it's something that should be on our key takeaway that it should be implemented because it's fantastic. Thank you.

And Sarah, just to get back onto the preparing a patient for trastuzumab deruxtecan in particular, what testing needs to be obtained prior to starting?

Sarah Tangerini: Sure. I think before even talking about what testing is needed prior to starting treatments, it's important to know the common toxicity and side effects that are to be expected while on treatment, because then we know what to look for prior to starting the treatment. Common symptoms of that patient's experience while on trastuzumab deruxtecan include neutropenia, so low white blood cell count, thrombocytopenia, and then cardio toxicity is one of the more common side effects that we don't always see in other therapies, which is specifically left ventricular dysfunction.

We can also see pneumonitis, elevated liver function tests, alopecia. And then some more common side effects that we see with a standard of care chemotherapy: decreased appetite, nausea, vomiting, diarrhea, constipation, fatigue, sometimes headaches and dry eyes, cough, shortness of breath, rash, and infusion reactions. It's important to note these before starting treatment. And then so we know what to look for to see if a patient has a history that might put them at risk for having more increased side effects while on treatment.

Specifically with trastuzumab deruxtecan prior to starting therapy, we like to obtain a detailed patient history including smoking status, and if they've had any previous interstitial lung disease. Because while on therapy, they may be at risk for developing pneumonitis from the treatment, so it's important to note if they have any baseline exposure to interstitial lung disease.

And then also, any side effects that they may have experienced from first line treatment and if any of these side effects are ongoing. For example, if someone had experienced pancytopenia on a standard of care chemotherapy, it's important to note if they have ongoing anemia or thrombocytopenia or neutropenia, because they are likely to experience this on trastuzumab deruxtecan. It's important to know that we'll have to monitor these labs closely while on treatment.

While on treatment, at a baseline, we like to specifically look at a CBC, a complete blood count and a complete metabolic panel, which will help us to monitor for the bone marrow suppression and for any electrolyte abnormalities, any abnormal baseline liver, or kidney function as well. And then, in terms of looking at the left ventricular dysfunction, we like to obtain an echocardiogram prior to starting treatment to check for baseline left ventricular ejection fraction. And we also like to get a baseline CT scan to assess the extent of the patient's disease prior to starting treatment.

So then, I also wanted to take a moment to just discuss management while patients are on the treatment, not just prior to starting treatment of what is needed before starting, but also what we need to monitor while on treatment. Before starting treatment, I also do like to discuss dosing schedule with our patients. So in our lung cancer patients, the approved dose is actually 5.4 milligrams per kilogram once every three weeks until disease progression or unacceptable toxicity. I like to review this with our patients prior to starting treatment and let them know this is the schedule that they should expect coming in for treatment.

I also like to let them know that if they do experience a side effect to treatment, depending on the severity in the grade, there is the option for dose reductions. And in the clinical trials, they found that there can be two dose reductions. One can be 4.4 milligrams per kilogram, so that would be the first dose reduction. And if a patient can't tolerate that dose, the second dose reduction is 3.2 milligrams per kilogram.

If any further dose adjustments are required, so if patients can't tolerate the 3.2 milligram per kilogram dose, then we generally discontinue treatment because they found that treatment at a lower dose was not effective. Before starting patients on treatment, we want to make sure that they have a good left ejection fraction prior to starting, because they may run into some issues while on treatment. Generally speaking, we like patients to have left ventricular ejection fractions greater than 50% prior to starting treatment and we want to avoid giving treatment and patients with LVEF less than 50%.

However, there is an exception to this. If patients have a cardiologist and they follow their cardiologist closely and we have clearance from cardiology, we are allowed to give treatments if patients LVEF is 40% to 50%. But it's something that we would want to monitor them closely while on treatment. While on treatment, what do we want to monitor for? We want to monitor their CBCs, their BMPs, and we want to look specifically for elevated liver function tests.

We want to assess left ventricular ejection fraction periodically while on treatment. We want to evaluate pregnancy status prior to starting therapy. In patients who could become pregnant, it's important to note that we should be obtaining pregnancy status prior to starting therapy. We want to monitor for signs and symptoms of interstitial lung disease and pneumonitis while on treatment. We want to look for skin rashes, make sure they're not experiencing any skin rashes. And we also want to monitor for infusion reactions.

Stephanie McDonald: I was just wondering because it got me thinking. I just had a question in general just before we conclude. Dr. Florez, is there any role in getting baseline pulmonary function tests on patients that we identify that are at risk? It's hard, our patients mostly can be smokers and are. I don't know if that really sets them up for a higher risk of developing pneumonitis on some of these drugs.

But is there any information that you can provide or anything, in your understanding, that there's, there would possibly be event of it for any pulmonary function test prior to the development of any signs of pneumonitis or ILD?

Dr. Narjust Florez: You can get pulmonary functional as a baseline, but the most important thing is to have the baseline of the patient's lung capacity. Because we know that some patients have excellent functional capacity, excellent pulmonary function tests, but their lung capacity is reduced. So how long before they get shortness of breath, how much exercise they can do.

Because the grade one versus the grade two for ILD […] is the capacity of doing activities of daily living. If you cannot get a pulmonary function test, make sure to document before starting therapy, the lung capacity. How many flies or steps, how many blocks can you do? You're evaluating the patient, the patient can have a point of reference.

Stephanie McDonald: Awesome, thank you. Thank you, Sarah. Sorry.

Sarah Tangerini: Oh, no problem. I just want to take a quick moment to discuss key clinical takeaways from this case study. For one, it's important [...] the importance of implementing standardized chemotherapy teaching sessions with our patients and families prior to initiation of new therapies such as trastuzumab deruxtecan. Spending a dedicated time to educate our patients on the side effects associated with their treatment, and review the importance of when to call for any new or worsening symptoms.

And then, to also confirm that the patient has an appropriate antiemetic regimen to use as needed for nausea. I didn't really talk about this in detail, but this therapy can be fairly nauseating, so it is important to make sure that they have an appropriate antiemetic regimen prior to starting treatment. A lot of the time, we follow the same regimen that they've used on their standard of care treatment. If something has worked for them in the past, I tend to try and stick with that. However, there's always options to increase antiemetics if needed while on treatment.

It's important to monitor for neutropenia while patients are on treatment, so advising our patients for the possibility of developing this neutropenia and to call immediately, particularly in association with any signs of infection. We generally tell our patients to monitor for fevers greater than a 100.4 degrees Fahrenheit at home and to call us immediately if they do experience a fever while on treatment.

Also, understanding that this treatment can cause left ventricular dysfunction, so it's important to always assess LVEF prior to initiation of the trastuzumab deruxtecan, and at regular intervals during treatment and as clinically indicated. Advising our patients to contact us immediately for any of the following: new onset worsening shortness of breath, cough, fatigue, swelling of the ankles, palpitations, sudden weight gain, dizziness, loss of consciousness.

These are all warning signs that there may be something going on with their heart, so we would want them to monitor for these things at home and call us immediately if they experience this. Obtaining a baseline echo or MUGA, and typically once every three months while on treatment or is clinically indicated. If a patient is asymptomatic while on treatment, I generally just follow the every three month rule. But if a patient does experience, say, swelling of the legs or new onset shortness of breath with exertion, then I may want to obtain an echo sooner than the three month interval. And then, to permanently discontinue treatment in patients with symptomatic congestive heart failure is a given. We never want to put patients at risk or harm them any further if they are experiencing these symptoms.

And finally, interstitial lung disease and pneumonitis can happen while on this treatment, including fatal cases. It's really important for our patients to monitor for risks of severe or fatal interstitial lung disease. And advising our patients to contact their healthcare provider immediately for any of the following symptoms: cough, shortness of breath, fever, or other new or worsening respiratory symptoms. Monitoring for these things is very important.

And then also, to permanently discontinue therapy in all patients with grade two or higher interstitial lung disease and pneumonitis. These are the big key clinical takeaways of what we need to monitor while patients are that trastuzumab deruxtecan. But otherwise, just having our patients keep a very close line of communication is key. I like to tell my patients, "If you have any concerns, even if you don't think it's related to treatment, please call and let us know," because I would prefer them to be a little bit over vigilant in monitoring their side effects from treatment rather than under report.

Stephanie McDonald: Excellent. I agree. I know the key is communication. We can't stress that enough. And I think telling our patients that and giving them the information to contact us is really ... and going over those key side effects and what to look out for. And like you said, communication is key. Thank you. Thank you both. This brings us to the end of this case. Please see the other segments for further discussion on HER2 mutant non-small cell lung cancer or visit advanced practitioner.com. Thank you.